Combined Rg1 and adipose-derived stem cells Alleviate DSS-induced colitis in a mouse model

Abstract Background Inflammatory bowel diseases (IBDs) including Crohn's disease and ulcerative colitis are chronic inflammatory disorders that can affect the entire gastrointestinal tract and the colonic mucosa, no medical or surgical cure for IBD, and all have side effects that limit their use, exhibit a high necessity for new therapeutic strategies. Adipose-derived stem cells (ADSC) therapy represents a promising option for the treatment of IBD. Rg1 Previous study indicated that ginsenoside (Rg1) can ameliorate inflammatory disease such as colitis by inhibiting the binding of LPS to TLR4 on macrophages and restoring the Th17/Treg imbalance [1]. In this study, we investigated whether Rg1 can enhance the effect of ADSC on DSS-induced colitis in a mouse model. Methods Mice with dextran sulfate sodium-induced colitis were injected intravenously with ADSC and administered with Rg1 by gavage. Body weight change, colon length, H&E staining were used to evaluate colon inflammation severity in a DSS-induced colitis Serum were collected for Cytokine detection by ELISA. The proportion and FMI of immune cells in spleen were analyzed by flow cytometry. Stool DNA was extracted for 16S rRNA gene sequencing. Results Rg1 and ADSC showed significantly ameliorated colon inflammation, such as body weight loss, shortening of colon length, histology score. Rg1 and ADSC treatment downregulated the level of proinflammatory cytokines, including IL-1β, TNF-α, IL-6, IL-4 and IL-17A and upregulated the immunosuppressive cytokine IL-10 in serum. We observed that the structure of the microbial community in Rg1 + ADSC group were significantly changed compared to that of ADSC and Rg1 groups, respectively. Additionally, Rg1 and ADSC treated selectively upregulated the percentage of spleen regulatory T (Treg) cells as well as downregulated the frequency of T helper type 17 (Th17) cells, ameliorating the Treg/Th17 balance to maintain intestinal homeostasis. Furthermore, we found the combination of ADSC + Rg1 groups showed more efficiently than that of ADSC and Rg1 alone, respectively, which indicates that the regulation effect of Rg1 on gut microbiome may enhance the effects of ADSCs in restoring immune balance. Conclusions Our study indicated that the combination of Rg1 and ADSC can alleviate dextran sulfate sodium-induced colitis more efficiently than that of ADSC alone, Rg1 can enhance the effect of ADSC on DSS-induced colitis in a mouse model.